Lactoferrin (LF) is an iron-binding protein found in mucosal secretions, tears, breast milk, and neutrophils. It has well- characterized bacteriostatic and bactericidal activity and has been suggested to play a role in protecting mucosal membranes and breast-fed infants from infection. Preliminary studies suggest that LF exerts an antiviral effect as well. This proposal will characterize the inhibitory effect of Lf on herpes simplex virus, type 1. LF binding to the virus will be investigated, and the specific site and mechanism of antiviral activity will be determined. The effect of Lf on virus-infected cells will be studied. In addition, the contribution of Lf to the antiviral properties of mucosal secretions (saliva in this study) will be evaluated. Lf will be tested in combination with other antimicrobial salivary proteins for a possible synergistic antiviral effect. Finally, Lf will be tested against other viruses in order to gain an idea of the spectrum of Lf antiviral activity. As a result of this investigation, a newly described antimicrobial effect of Lf will be characterized and will be suggestive of another mechanism of innate immunity against infection. In addition, this investigation will provide scientific training for a doctoral graduate student and an opportunity to present his/her research at a national science meeting and submit at least one paper for publication.